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学者姓名:杨桂红
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甲型流感病毒(IAV)编码的基质蛋白1(M1)通过调控E3泛素连接酶ITCH介导的泛素化修饰反应拮抗宿主的抗病毒免疫反应。本课题前期研究表明,神经介素B(NMB)和其受体NMBR具有抑制IAV的先天性免疫应答反应的作用,但二者对IAV感染诱导的E3泛素连接酶ITCH和M1表达的影响如何,尚未见报道。因此,本文采用外源性NMB及H9N2亚型禽流感病毒刺激模型,适时干扰和过表达NMBR,分别从体内外水平分析NMB和NMBR对ITCH和M1蛋白的表达水平的影响。结果显示:添加外源性NMB和过表达NMBR均可显著抑制H9N2亚型禽流感病毒感染的A549细胞和小鼠肺组织中ITCH表达;与之相对,干扰NMBR表达则可显著促进A549细胞和小鼠肺组织中ITCH表达;此外,NMB和NMBR对H9N2亚型禽流感病毒感染诱导的ITCH的表达趋势与M1蛋白的表达呈现正相关。以上结果表明,NMB和NMBR可通过调节ITCH的表达而影响H9N2编码的M1蛋白的表达,从而发挥抗H9N2亚型禽流感病毒感染的先天性免疫反应。
Keyword :
E3泛素连接酶ITCH E3泛素连接酶ITCH H9N2流感病毒 H9N2流感病毒 神经介素B 神经介素B 神经介素B受体NMBR 神经介素B受体NMBR
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| GB/T 7714 | 田世茂 , 田珂 , 刘玉钤 et al. 神经介素B和受体对H9N2亚型流感病毒感染诱导的ITCH表达的影响 [J]. | 畜牧兽医学报 , 2025 , 56 (04) : 1834-1842 . |
| MLA | 田世茂 et al. "神经介素B和受体对H9N2亚型流感病毒感染诱导的ITCH表达的影响" . | 畜牧兽医学报 56 . 04 (2025) : 1834-1842 . |
| APA | 田世茂 , 田珂 , 刘玉钤 , 辜晴新 , 沈昀知 , 张骋怀 et al. 神经介素B和受体对H9N2亚型流感病毒感染诱导的ITCH表达的影响 . | 畜牧兽医学报 , 2025 , 56 (04) , 1834-1842 . |
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Long non-coding RNAs (lncRNAs) have been recognized for their crucial roles in the replication processes of various viruses. However, the specific functions and regulatory mechanisms of many lncRNAs in influenza A virus (IAV) pathogenesis remain poorly understood. In this study, we identified lncRNA THRIL and observed a significant reduction in its expression following IAV infection in A549 cells. The treatment of cells with the viral mimic poly (I:C), or with type I and type III interferons, resulted in a substantial decrease in THRIL expression. Furthermore, THRIL overexpression significantly enhanced IAV replication, while its silencing markedly reduced IAV replication. Additionally, IAV infection led to notable reductions in the expression levels of type I and type III interferons in cell lines overexpressing THRIL compared to control groups; conversely, cell lines with THRIL knockdown exhibited significantly higher interferon levels than control groups. Moreover, THRIL was found to inhibit the expression of several critical interferon-stimulated genes (ISGs), which are essential for an effective antiviral response. Notably, our findings demonstrated that THRIL impaired the activation of IRF3, a key transcription factor in the interferon signaling pathway, thereby suppressing host innate immunity. These results highlight THRIL's potential as a therapeutic target for antiviral strategies.
Keyword :
influenza A virus influenza A virus innate immunity innate immunity IRF3 IRF3 long non-coding RNAs long non-coding RNAs THRIL THRIL
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| GB/T 7714 | Chen, Mengying , Hu, Jingyun , Zhou, Xinni et al. Long Non-Coding RNA THRIL Promotes Influenza Virus Replication by Inhibiting the Antiviral Innate Immune Response [J]. | VIRUSES-BASEL , 2025 , 17 (2) . |
| MLA | Chen, Mengying et al. "Long Non-Coding RNA THRIL Promotes Influenza Virus Replication by Inhibiting the Antiviral Innate Immune Response" . | VIRUSES-BASEL 17 . 2 (2025) . |
| APA | Chen, Mengying , Hu, Jingyun , Zhou, Xinni , Gao, Ming , Li, Ning , Yang, Guihong et al. Long Non-Coding RNA THRIL Promotes Influenza Virus Replication by Inhibiting the Antiviral Innate Immune Response . | VIRUSES-BASEL , 2025 , 17 (2) . |
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Neuromedin B (NMB) and its receptor NMBR constitute a neuropeptide system implicated in various physiological processes. While previously associated with innate immunity, their precise antiviral action against influenza A virus (IAV) infection have remained poorly defined. Here, we elucidate the function of the NMB/ NMBR axis in the host defense against H9N2 influenza virus. We demonstrate that NMB treatment and NMBR overexpression potentiate IFN-beta production and restrict viral replication in H9N2-infected A549 cells and mouse lungs. Conversely, NMBR knockdown compromises the antiviral response, diminishing IFN-beta expression and enhancing viral propagation. We further show that NMB/NMBR signaling targets the viral non-structural protein 1 (NS1) by upregulating the E3 ubiquitin ligase TRIM25. Mechanistically, NMB/NMBR activation engages a positive feedback loop with the retinoic acid-inducible gene I (RIG-I) pathway, reinforcing RIG-I activation through enhanced K63-linked ubiquitination while transcriptionally repressing the deubiquitinase CYLD. Consequently, this augmented signaling potentiates the JAK-STAT1 pathway, leading to increased STAT1 phosphorylation and elevated expression of interferon-stimulated gene 15 (ISG15). Our findings establish that the NMB/NMBR axis confers protection against H9N2 IAV by amplifying RIG-I-mediated innate immunity and facilitating NS1 suppression, revealing a pivotal neuroimmune mechanism and suggesting a promising target for developing broad-spectrum, host-directed therapeutics against IAV.
Keyword :
Innate antiviral Immunity Innate antiviral Immunity Neuromedin B Neuromedin B NMBR NMBR RIG-I RIG-I
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| GB/T 7714 | Yang, Guihong , Tian, Shimao , Yang, Jinyu et al. Neuromedin B and its receptor NMBR inhibit H9N2 infection [J]. | VETERINARY MICROBIOLOGY , 2025 , 312 . |
| MLA | Yang, Guihong et al. "Neuromedin B and its receptor NMBR inhibit H9N2 infection" . | VETERINARY MICROBIOLOGY 312 (2025) . |
| APA | Yang, Guihong , Tian, Shimao , Yang, Jinyu , Tang, Yubing , Tian, Ke , Wang, Song et al. Neuromedin B and its receptor NMBR inhibit H9N2 infection . | VETERINARY MICROBIOLOGY , 2025 , 312 . |
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神经介素B(NMB)及其G蛋白偶联受体(NMBR)发挥的抗甲型流感病毒免疫反应,以及甲型流感病毒感染诱导细胞程序性死亡配体1(PD-L1)高表达均与NF-κB信号通路有直接关系,而NF-κB信号通路的激活受ERK信号通路的调控。为深入探究NMB与NMBR调节H9N2亚型流感病毒感染诱导PD-L1上的作用,本研究以H9N2亚型流感病毒为模式毒株,基于NMBR干扰和过表达细胞系、PD-L1干扰和过表达细胞系以及C57BL/6小鼠,采用RT-PCR和Western blot方法分析NMB与NMBR对PD-L1表达变化以及ERK磷酸化的影响。结果显示:H9N2亚型流感病毒感染诱导的NMBR和PD-L1表达之间存在着负调控的关系,外源性NMB可以有效激活小鼠体内NMBR的表达,进而抑制PD-L1表达,NMB与NMBR也能影响H9N2感染诱导的ERK磷酸化水平。综上,H9N2亚型流感病毒感染诱导表达的NMB与NMBR通过ERK信号通路调节PD-L1的表达而发挥抗流感病毒作用,将为深度剖析宿主-甲型流感病毒之间的互作关系提供新的科学依据。
Keyword :
H9N2亚型 H9N2亚型 流感病毒 流感病毒 神经介素B 神经介素B 神经介素B受体 神经介素B受体 细胞程序性死亡配体1 细胞程序性死亡配体1
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| GB/T 7714 | 李春雨 , 田世茂 , 孔迎迎 et al. 神经介素B及受体NMBR和PD-L1在H9N2亚型流感病毒感染过程中的相互作用研究 [J]. | 畜牧与兽医 , 2024 , 56 (01) : 65-70 . |
| MLA | 李春雨 et al. "神经介素B及受体NMBR和PD-L1在H9N2亚型流感病毒感染过程中的相互作用研究" . | 畜牧与兽医 56 . 01 (2024) : 65-70 . |
| APA | 李春雨 , 田世茂 , 孔迎迎 , 陈灿辉 , 田也 , 刘莎莎 et al. 神经介素B及受体NMBR和PD-L1在H9N2亚型流感病毒感染过程中的相互作用研究 . | 畜牧与兽医 , 2024 , 56 (01) , 65-70 . |
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STATs蛋白在宿主抗病毒应答中具有重要功能,但对其在病毒感染早期的作用研究不多。为确定STATs蛋白在病毒感染早期的激活,本文采用甲型流感病毒H1N1亚型的不同毒株(WSN和PR8)和伪狂犬病毒(PRV)分别感染细胞或基因敲除小鼠,利用Western blotting分析STAT1和STAT3酪氨酸位点的磷酸化水平。结果显示,病毒感染早期阶段的干扰素等细胞因子产生时,可直接诱导STAT1和STAT3的激活。该结果表明非细胞因子依赖性早期抗病毒的天然免疫应答反应的存在,不仅为阐明病毒-宿主互作的分子基础提供新的理论依据,也为筛选新型抗流感病毒药物靶标提供了新思路。
Keyword :
STATs蛋白 STATs蛋白 抗病毒天然免疫 抗病毒天然免疫 早期激活 早期激活 甲型流感病毒(IAV) 甲型流感病毒(IAV)
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| GB/T 7714 | 陈灿辉 , 周文卓 , 李春雨 et al. 流感等病毒感染过程中STATs蛋白非细胞因子依赖性的早期激活 [J]. | 江西畜牧兽医杂志 , 2023 , 4 (02) : 15-18 . |
| MLA | 陈灿辉 et al. "流感等病毒感染过程中STATs蛋白非细胞因子依赖性的早期激活" . | 江西畜牧兽医杂志 4 . 02 (2023) : 15-18 . |
| APA | 陈灿辉 , 周文卓 , 李春雨 , 田也 , 陈秉一 , 陈吉龙 et al. 流感等病毒感染过程中STATs蛋白非细胞因子依赖性的早期激活 . | 江西畜牧兽医杂志 , 2023 , 4 (02) , 15-18 . |
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神经介素B(neuromedin B,NMB)及受体(NMB receptor, NMBR)通过NF-κB信号通路参与抑制甲型流感病毒(influenza A virus, IAV)H1N1亚型(IAV/H1N1)的感染。但关于NMB和NMBR对NF-κB信号通路相关泛素蛋白酶的调控如何,尚未见报道。为探究NMB和NMBR调控IAV诱导的NF-κB信号通路相关的泛素蛋白酶表达的影响,本研究基于IAV/H9N2感染sh-NMBR细胞与NMB刺激的A549细胞,采用RT-PCR、qRT-PCR及Western blot(WB)分析NMB和NMBR对H9N2感染引起的NF-κB信号通路相关的E3泛素连接酶Mind bomb-2(MIB2)和Ring Finger Protein 8(RNF8)及去泛素蛋白酶Cylindromatosis(CYLD)的表达变化。结果显示:H9N2感染sh-NMBR细胞中,RNF8和CYLD表达增加,MIB2表达和P65磷酸化水平降低;NMB激活A549细胞中NMBR的表达后,诱导细胞中RNF8和CYLD的表达水平下降,MIB2表达和P65磷酸化水平增加。结果表明:NMB和NMBR通过调控IAV/H9N2感染诱导的泛素蛋白酶的表达和P65活性,从而影响IAV/H9N2感染激活的NF-κB信号通路的功能,该结果为深入研究NMB和NMBR抑制甲型流感病毒感染的作用机制提供了理论基础。
Keyword :
E3泛素连接酶 E3泛素连接酶 IAV/H9N2亚型 IAV/H9N2亚型 P65磷酸化 P65磷酸化 神经介素B 神经介素B 神经介素B受体 神经介素B受体
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| GB/T 7714 | 田世茂 , 万乾晖 , 许晓东 et al. H9N2亚型流感病毒感染过程中神经介素B及受体对NF-κB信号通路泛素酶的调控 [J]. | 畜牧兽医学报 , 2023 , 54 (07) : 3118-3126 . |
| MLA | 田世茂 et al. "H9N2亚型流感病毒感染过程中神经介素B及受体对NF-κB信号通路泛素酶的调控" . | 畜牧兽医学报 54 . 07 (2023) : 3118-3126 . |
| APA | 田世茂 , 万乾晖 , 许晓东 , 孔迎迎 , 田珂 , 唐钰冰 et al. H9N2亚型流感病毒感染过程中神经介素B及受体对NF-κB信号通路泛素酶的调控 . | 畜牧兽医学报 , 2023 , 54 (07) , 3118-3126 . |
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The clinical benefits of targeting programmed death-ligand 1 (PD-L1) in various cancers represent a strategy for the treatment of immunosuppressive diseases. Here, it was demonstrated that the expression levels of PD-L1 in cells were greatly upregulated in response to H1N1 influenza A virus (IAV) infection. Overexpression of PD-L1 promoted viral replication and downregulated type-I and type-III interferons and interferon-stimulated genes. Moreover, the association between PD-L1 and Src homology region-2, containing protein tyrosine phosphatase (SHP2), during IAV/H1N1 infection was analyzed by employing the SHP2 inhibitor (SHP099), siSHP2, and pNL-SHP2. The results showed that the expressions of PD-L1 mRNA and protein were decreased under SHP099 or siSHP2 treatment, whereas the cells overexpressing SHP2 exhibited the opposite effects. Additionally, the effects of PD-L1 on the expression of p-ERK and p-SHP2 were investigated in PD-L1-overexpressed cells following WSN or PR8 infection, determining that the PD-L1 overexpression led to the decreased expression of p-SHP2 and p-ERK induced by WSN or PR8 infection. Taken together, these data reveal that PD-L1 could play an important role in immunosuppression during IAV/H1N1 infection; thus, it may serve as a promising therapeutic target for development of novel anti-IAV drugs.
Keyword :
cytokines cytokines inflammation inflammation influenza A virus H1N1 subtype influenza A virus H1N1 subtype programmed death ligand 1 programmed death ligand 1 SHP2 SHP2 virus replication virus replication
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| GB/T 7714 | Ning, Hongya , Chiu, Shih-Hsin , Xu, Xiaodong et al. The Immunosuppressive Roles of PD-L1 during Influenza A Virus Infection [J]. | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES , 2023 , 24 (10) . |
| MLA | Ning, Hongya et al. "The Immunosuppressive Roles of PD-L1 during Influenza A Virus Infection" . | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 24 . 10 (2023) . |
| APA | Ning, Hongya , Chiu, Shih-Hsin , Xu, Xiaodong , Ma, Yanmei , Chen, Ji-Long , Yang, Guihong . The Immunosuppressive Roles of PD-L1 during Influenza A Virus Infection . | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES , 2023 , 24 (10) . |
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Pseudorabies virus (PRV) infection could cause severe histopathological damage via releasing multiple factors, including cytokines, peptides, etc. Here, peptidomic results showed that 129 peptides were identified in PRV-infected mouse lungs and were highly involved in the process of PRV infection. The role of one down-regulated biological peptide (designated as AGDP) during PRV infection was investigated. To verify the expression profiles of AGDP in response to PRV infection, the expression level of the precursor protein of AGDP mRNA was significantly decreased in PRV-infected mouse lungs and cells. The synthesized AGDP-treating cells were less susceptible to PRV challenges than the controls, as demonstrated by the decreased virus production and gE expression. AGDP not only inhibited the expression of TNF-alpha and IL-8 but also appeared to suppress the extracellular release of high-mobility group box 1 (HMGB1) by inhibiting the output of nuclear HMGB1 in cells. AGDP could also inhibit the degradation of I kappa B alpha and the phosphorylation levels of P65 after PRV infection. In total, our results revealed many meaningful peptides involved in PRV infection, thereby enhancing the current understanding of the host response to PRV infection, and how AGDP may serve as a promising candidate for developing novel anti-PRV drugs.
Keyword :
AGDP AGDP cytokines cytokines inflammation inflammation peptidomic analysis peptidomic analysis Pseudorabies virus Pseudorabies virus virus replication virus replication
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| GB/T 7714 | Ma, Yijie , Tian, Shimao , Wan, Qianhui et al. Peptidomic Analysis on Mouse Lung Tissue Reveals AGDP as a Potential Bioactive Peptide against Pseudorabies Virus Infection [J]. | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES , 2022 , 23 (6) . |
| MLA | Ma, Yijie et al. "Peptidomic Analysis on Mouse Lung Tissue Reveals AGDP as a Potential Bioactive Peptide against Pseudorabies Virus Infection" . | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 23 . 6 (2022) . |
| APA | Ma, Yijie , Tian, Shimao , Wan, Qianhui , Kong, Yingying , Liu, Chang , Tian, Ke et al. Peptidomic Analysis on Mouse Lung Tissue Reveals AGDP as a Potential Bioactive Peptide against Pseudorabies Virus Infection . | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES , 2022 , 23 (6) . |
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The neuropeptide S (NPS) and its receptor (NPSR) represent a signaling system in the brain. Increased levels of NPS and NPSR have been observed in PK15 cells and murine brains in response to pseudorabies virus (PRV) infection, but it remains unclear whether elevated levels of NPS and NPSR are involved in the pathogenic process of PRV infection. In this study, the activities of both NPS and NPSR during PRV pathogenesis were explored in vitro and in vivo by reverse transcription polymerase chain reaction (RT-PCR), PCR, real-time quantitative RT-PCR (qRT-PCR), qPCR, TCID50, and Western blotting methods. NPSR-deficient cells were less susceptible to PRV infection, as evidenced by decreased viral production and PRV-glycoprotein E (gE) expression. In vitro studies showed that exogenous NPS promoted the expression of interleukin 6 (IL-6) mRNA but inhibited interferon beta (IFN-beta) mRNA expression in PK15 cells after PRV infection. In vivo studies showed that NPS-treated mice were highly susceptible to PRV infection, with decreased survival rates and body weights. In addition, NPStreated mice showed elevated levels of IL-6 mRNA and STAT3 phosphorylation. However, the expression of IFN-beta mRNA was greatly decreased after virus challenge. Contrasting results were obtained from the NPSR-irtreated groups, which further highlighted the effects of NPS. This study revealed that NPS-treated hosts are more susceptible to PRV infection than controls. Moreover, excessive IL-6/STAT3 and defective IFN-beta responses in NPS-treated mice may contribute to the pathogenesis of PRV.
Keyword :
Antagonist Antagonist Cytokines Cytokines Neuropeptide S Neuropeptide S NPSR NPSR Pseudorabies virus Pseudorabies virus
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| GB/T 7714 | Li, Chunyu , Ma, Yijie , Cai, Zifeng et al. Neuropeptide S and its receptor NPSR enhance the susceptibility of hosts to pseudorabies virus infection [J]. | RESEARCH IN VETERINARY SCIENCE , 2022 , 146 : 15-23 . |
| MLA | Li, Chunyu et al. "Neuropeptide S and its receptor NPSR enhance the susceptibility of hosts to pseudorabies virus infection" . | RESEARCH IN VETERINARY SCIENCE 146 (2022) : 15-23 . |
| APA | Li, Chunyu , Ma, Yijie , Cai, Zifeng , Wan, Qianhui , Tian, Shimao , Ning, Hongxia et al. Neuropeptide S and its receptor NPSR enhance the susceptibility of hosts to pseudorabies virus infection . | RESEARCH IN VETERINARY SCIENCE , 2022 , 146 , 15-23 . |
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<正>引言伪狂犬病是由伪狂犬病毒(Pseudorabies virus,PRV)是一种线性双链DNA病毒,属于疱疹病毒科,α-疱疹病毒亚科,能感染猪、牛、兔和鼠等哺乳动物以及各种野生动物[1,2]。近年来,由于PRV传播能力和致病力不断提高,导致原有疫苗免疫失败,给养殖业带来巨大灾难[3]。研究表明:动物感染PRV后,宿主的模式识别受体特异性识别病毒DNA,从而激活宿主天然免疫应答系统。
Keyword :
NPS NPS 伪狂犬病毒 伪狂犬病毒 神经肽 神经肽
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| GB/T 7714 | 马逸杰 , 蔡紫峰 , 万乾晖 et al. 神经肽S对伪狂犬病毒感染小鼠的体内作用研究 [C] //中国畜牧兽医学会动物传染病学分会第十九次全国学术研讨会 . 2021 . |
| MLA | 马逸杰 et al. "神经肽S对伪狂犬病毒感染小鼠的体内作用研究" 中国畜牧兽医学会动物传染病学分会第十九次全国学术研讨会 . (2021) . |
| APA | 马逸杰 , 蔡紫峰 , 万乾晖 , 田世贸 , 宁红涯 , 王松 et al. 神经肽S对伪狂犬病毒感染小鼠的体内作用研究 中国畜牧兽医学会动物传染病学分会第十九次全国学术研讨会 . (2021) . |
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